New Positron Emission Tomography (PET) Radioligand for Imaging 蟽-1 Receptors in Living Subjects

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• 作者：Michelle L. James ; Bin Shen ; Cristina L. Zavaleta ; Carsten H. Nielsen ; Christophe Mesangeau ; Pradeep K. Vuppala ; Carmel Chan ; Bonnie A. Avery ; James A. Fishback ; Rae R. Matsumoto ; Sanjiv S. Gambhir ; Christopher R. McCurdy ; Frederick T. Chin
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：October 11, 2012
• 年：2012
• 卷：55
• 期：19
• 页码：8272-8282
• 全文大小：416K
• 年卷期：v.55,no.19(October 11, 2012)
• ISSN：1520-4804

文摘

蟽-1 receptor (S1R) radioligands have the potential to detect and monitor various neurological diseases. Herein we report the synthesis, radiofluorination, and evaluation of a new S1R ligand 6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ([¹⁸F]FTC-146, [¹⁸F]13). [¹⁸F]13 was synthesized by nucleophilic fluorination, affording a product with >99% radiochemical purity (RCP) and specific activity (SA) of 2.6 卤 1.2 Ci/渭mol (n = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo autoradiography studies of [¹⁸F]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pretreatment with 1 mg/kg haloperidol (2), nonradioactive 13, or BD1047 (18) reduced the binding of [¹⁸F]13 in the brain at 60 min by 80%, 82%, and 81%, respectively, suggesting that [¹⁸F]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [¹⁸F]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects.